title: Interleukin-2-based therapy for metastatic renal cell cancer: the Cytokine Working Group experience, 1989-1997.
abstract: OBJECTIVE
  This article reviews long-term follow-up data from three phase II studies conducted by the Cytokine Working Group from 1989 to 1995 that evaluated various recombinant interleukin-2 (rIL-2) -based regimens in patients with metastatic renal cell cancer. Response rates, long-term response duration, and toxicity are compared.
  
  
  METHODS
  The Cytokine Working Group studies reviewed here investigated the safety and efficacy of two high-dose intravenous rIL-2-based regimens and two moderate-dose outpatient subcutaneous rIL-2-based regimens in patients with progressive metastatic renal cell cancer. A randomized phase II study, initiated in 1989, investigated the safety and efficacy of high-dose intravenous rIL-2 alone and high-dose intravenous rIL-2 plus recombinant interferon-alpha (rIFN-alpha). A second phase II study, initiated in 1992, tested the safety and efficacy of moderate-dose subcutaneous rIL-2 plus subcutaneous rIFN-alpha in the outpatient setting. The third trial, initiated in 1995, investigated a regimen consisting of the previous subcutaneous rIL-2 plus rIFN-alpha regimen alternating with intravenous bolus 5-fluorouracil (5-FU) plus subcutaneous rIFN-alpha. Median follow-up for these studies is 72 months, 48 months, and 24 months, respectively.
  
  
  RESULTS
  The overall response rates observed with each of these regimens were similar (17% with high-dose rIL-2 alone, 11% with high-dose rIL-2/rIFN-alpha, 17% with outpatient subcutaneous rIL-2/rIFN-alpha, and 16% with outpatient rIL-2/rIFN-alpha, plus 5-FU/rIFN-alpha). However, the high-dose rIL-2 regimen produced a 7% complete response rate, compared with 0%, 4%, and 4%, respectively, with each of the other regimens. Median response duration was also much longer with high-dose intravenous rIL-2 alone (53 months), compared with 7 months, 12 months, and 9 months, respectively, with each of the other regimens.
  
  
  CONCLUSIONS
  Complete response rate and response duration appear to favor the high-dose intravenous rIL-2 regimen. This will require verification in a randomized study comparing the best high-dose arm (rIL-2 alone) with the best outpatient regimen (rIL-2/IFN-alpha). The Cytokine Working Group is currently conducting such a study.
authors.affiliation: Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, New York 10467, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: M
authors.initials: M
authors.lastname: Atkins
authors.forename: R
authors.initials: R
authors.lastname: Fisher
authors.forename: G
authors.initials: G
authors.lastname: Weiss
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: F
authors.initials: F
authors.lastname: Aronson
authors.forename: J
authors.initials: J
authors.lastname: Sosman
authors.forename: M
authors.initials: M
authors.lastname: Lotze
authors.forename: M
authors.initials: M
authors.lastname: Gordon
authors.forename: T
authors.initials: T
authors.lastname: Logan
authors.forename: J
authors.initials: J
authors.lastname: Mier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2